I truly, truly hope this works as described, even partially, on humans. It is so frustrating to see someone who would be able to walk if only the signal could get to their lower extremities.
My grandfather is a paraplegic, and man how much I hope this isn't just faery dust.
Based on this stimulating Axon growth, it sounds like it might help to repair the damage caused by MS. That would be amazing news. Not a cure per se, but a way to actually treat symptoms rather than just surpressing. Worryingly, they mention a few neurodegenerative diseases but not MS.
BioNTech is working on a vaccine against MS that is supposed to untrain the immune system to no longer attack own tissue. It should at least slow progress of the disease and even seems to have allowed to reverse early damages in mice. Let’s keep our fingers crossed.
Through the years I've seen dozens and dozens of "cures" for "MS" in mice (I put MS in quotes because, at this point, I've grown skeptical that the induced encephalitis mouse model is all that helpful in predicting drug performance for humans with MS). The closest thing we have to a "cure" is actually a medication that's been on the market for a while, but it was used to treat certain types of blood cancer before they discovered that it works really well for MS too.
It's now available generically: Rituximab. There's another hack that Genentech was able to patent and approve for MS to produce Ocrelizumab, which does the same thing as Rituximab but costs an order of magnitude more. Because that's how the world of big pharma works.
In essence, wiping out your plasma cells (a.k.a. B cells or lymphocytes) seems to stop MS in its tracks. Where my neurologist would typically see 2 or 3 new lesions in any given patient per year, instead now my neurologist is seeing 2 or 3 new lesions per year in the population of all their RRMS patients who are on Rituximab (or Ocrelizumab). And it turns out the immune system can get along pretty well with all the other cells types it has, such as T cells.
Just noting that -mab therapeutics are not synthesized directly, they are produced in cloned cell lines. It’s practically impossible for one pharma company to replicate another companies -mab, since they will never have access to the exact cell line used to manufacture the original. Also, Rituximab hasn’t been fully characterized, hence the discovery of new uses. There is no such thing as generic when it comes to -mab therapeutics.
Point is, the cost to create Ocrelizumab may be legitimately higher than Rituximab.
Interesting point raising regulatory questions for sure.
Should the government compel drug companies to share their cell lines to preserve the same market dynamics as generic drugs once a monoclonal antibody line product hits the timeline to go generic?
After all, otherwise it would be somewhat similar to a drug company rejecting to share the chemical synthesis pathway and precursors saying "an ex-employee built this chemical synthesis machinery and we just put the raw ingredients and comes out the drug from the other end".
But I am guessing for generic drugs, the generic manufacturers are expected to come up with their own synthesis pathway anyway and the original manufacturer has no obligations to help.
Well, that’s the thing, you can’t make a generic version of these drugs because you can’t fully characterize the structure. They are just way too big and complicated, which is scary because a single difference in a glycosolation site can induce an extreme immunogenic response.
Best the FDA can do is allow biosimilars and subject them to significantly more testing, which increases the cost 100x (compared to a traditional generic).
Fetal stem cells also apparently can stop degeneration from MS abd regress it (heal the damage) if disease progression hasn't damaged the body's healing mechanisms too much; emcell.com
Do I want to know how they get mice with severe spinal cord injuries to test on? I'm guessing it's exactly what I think it is, but I'm wondering if there's another way that it happens.
It’s what you think it is, and it happens to more than just mice. I toured a bioengineering lab where they were actively severing the spines of chimpanzees to perform fiber rerouting experiments. I think the normal citizen never thinks much if at all about this kind of thing because they’re never exposed to it. A few researchers have opened up to me personally about their personal psychological trauma caused by involvement with animal experimentation. A couple PhD candidates I know changed fields entirely. One to ecology and another to environmental engineering. I personally moved forward with bioinformatics.
Edit: that isn’t to say that this result isn’t exciting for human welfare. We’ll see if it translates…
I was originally a biology major and only ended up finishing the minor in part because of this. We had a lab assignment to do a live vivisection of a limpet to be able to view some of the circulatory systems in play in a still-living creature. We were supposed to paralyze them first, but whatever I did was incorrect. That thing was writhing and squirming and trying to get away and showing all the outward physical signs of being in pain the entire time.
Limpets don't even have brains, just cerebral ganglia, so it's likely it isn't really a sentient creature that has any conscious awareness of what is happening to it, but man, that scarred me. It felt like I was torturing something horribly and I knew that was not the career for me. There is no way I'd have ever been able to do that to a mouse.
This is absolutely in the moral gray. The greater good, lesser of two evils, however you want to describe it whether it's right or wrong will get down to your personal beliefs.
I had a family member involved in a cancer research that used mice and although he admitted it was sad, he did call them heroes. Understandably, I don't think that satisfies anyone strongly aligned with animal rights. In many other sciences we've been able to use simulation as a first step, but that is still out of our reach for biological systems.
I'm sorry you were downvoted for asking that. I think it's a fair issue to raise. Assuming the mice are intentionally injured to allow testing, it seems reasonable, to me, to question the ethics of that. Of course it's easy to say "they're just mice, who cares?" but it's not wrong to ask "they're living creatures as well, shouldn't we care?" I expect the response to be "it's justified given the benefits we derive for humans, based on this mouse based research", and probably most people would agree with that. But perhaps not everyone would.
Also consider the number of really scary books/movies out there rooted in the idea of "medical utilitarianism." For one example, this issue is addressed in a show called Biohackers that I just started watching. And even in real life, people have tried to justify a lot of really sketchy stuff over the years, in the name of "the greater good".
We do have an alternative to animal testing. We can use humans who are desperate enough to volunteer to a medical experiment knowing that it might not work and could potentially make things worse. The purpose of animal testing in situations like this is to catch early problems before the final human testing. Computer simulation can do a lot to minimize the need for animal testing, but I don't think we are there yet where we can go directly from a simulation to human testing.
I do not however like to view it as medical utilitarianism. The testing will happen regardless if the test subject are human or mice, because people do still want the medical cures. People are however less sad if an experiment accidentally killed a bunch of mice than if a bunch of human test subjects died. Historically people tend to use military service men as test subjects, which is why much of medical knowledge is based on test subjects of a specific gender (male) and age group (20-35). Not that long ago (~1950) people also used people with mental disabilities and orphans. Going just a decade earlier and people used prisoners and war and people deemed unwanted. Hopefully computers will one day replace the need for testing.
> We do have an alternative to animal testing. We can use humans who are desperate enough to volunteer...
This situation would presumably only arise because somebody else previously made the decision not to perform that experiment on an animal, but instead wait until a human suffers enough to become desperate enough to volunteer. That decision resulted in human suffering (albeit in the form of the trolley problem). Was that decision acceptable? How much human suffering, and/or how many humans suffering, is equivalent to one animal? Does sapience make a difference to this calculation?
I'm not saying this makes animal testing OK. My point is just that testing only on human volunteers isn't a magical solution to this ethical problem.
I agree, its not a magical solution. Some might even call it exploiting to use people when they are at their most desperate point in their lives, and for pediatric research it would basically involve a situation where its the parents that agrees to the medical experiment.
Its a difficult decision to make, experimenting on either animals or people.
The the answer in the science and medical communities is Almost Never "they're just mice, who cares"
That's fair. My comment above was maybe overly glib in that sense. But I was just trying to capture the general spirit of the thing, not write an essay, due to limits of time, interest, and knowledge on my part.
It's funny how this cost benefit calculation is considered valid when applied to research on mice, but any such calculation used to try to justify research on humans would give a "divide by 0" error. I think there's an inconsistency there somewhere.
"it can't be done any other way" strikes me as pretty thin. Whereas we may not be able to conceive of another way at this point in time, it does no good to imagine that this condition will continue in perpetuity.
I'm curious if you can elaborate on, "they're living creatures, shouldn't we care?".
No, because I'm not saying that is a position I personally hold. I'm merely presenting it as a position that I know that (some) people do hold.
My position here is, roughly speaking, "this (intentionally injuring mice or other animals) is an issue where there is a legit discussion to be had around the ethics of same." Of course I have my own opinion, but I don't really care to get into it. I just didn't think that the parent poster needed to be downvoted for raising the question.
Perhaps “living creatures” is a bit broad if taken too literally, but in context here it seems like the implied topic is clearly animals. One reason the base assumption is caring is because we have laws against harming, torturing or being cruel to animals, and laws against killing some animals. Another reason to care is the growing scientific and public awareness that animals have intelligence, consciousness, and feelings. A third reason is that we have a base assumption about caring for humans, both socially and physiologically, and seeking a moral consistency might automatically lead to the reasonable question “shouldn’t we care about animals too?”.
Since your question implies some, are there reasons that we shouldn’t care about animals or other living creatures?
I'll try: we have absolutely no idea to what degree any given living thing can feel pain, in the subjective sense. We know that mice, for example, react in a way that looks like pain to painful stimulus, but we don't know if there is anything that it feels like to be a mouse in pain. We care when humans feel pain, in a large part because we know, almost for certain (although not quite), that they are feeling pain... why should the same not extend to a creature that may be having a similar experience?
Not the poster obviously, but I'm going to give my two cents on this.
Obviously the phrase "they're living creatures" is a bit vague on this; bacteria and molds (and arguably viruses) are also living creatures but I don't think anyone considers it genocide to disinfect your counter with alcohol or something. I think we generally start drawing lines with animals.
Even within the scope of animals, I think we can still make reasonable concessions on things that are of sufficiently low intelligence to where we're not even 100% sure they feel pain in the same way that we do. Do I care if a mosquito suffers? No, not really, they're annoying dangerous little critters who aren't really having a lot of intelligent thought.
However, when we start getting into mammals (and possibly birds), I think it starts getting into more questionable territory. Most mammals (as far as I know) do have enough neural development to feel pain, to feel fear, and actually suffer in ways not completely dissimilar to humans. Since mice are mammals, there is an argument to be made that if we're hurting them, it's adding a lot of pain to the world.
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To be clear, I'm somewhat in the camp of "they're just mice, I care about helping humans more". I just wanted to play devil's advocate for a bit.
Living creatures might be too much (see bacteria), but if you think we should care about other people - it follows that we should also care about other creatures that can feel and think. Mammals certainly qualify.
> but if you think we should care about other people - it follows that we should also care about other creatures that can feel and think
It doesn't automatically follow. I can entirely correctly, subjectively decide which living things I want to care about and which I do not. I can separate living things by a hierarchy of importance. Which is exactly what we do all the time with other people and our relationships to them (example: hey HN, let me know how much you love Donald Trump and where he ranks on your hierarchy of importance).
I don't care about mice. I care about puppies (insert reasons here). That is not an irrational position. It's entirely subjective either direction. Any attempt to apply logic or science to the premise is inherently absurd. What we each value and why is subjective, it's personal; it inherently can't be objective. Rat and mice fans might likely pick those over puppies or kittens for example, due to their personal experiences and their hierarchy of values.
No, I wouldn't kill or injure the mice myself for a living. I think it's grotesque.
I wouldn't perform abortions for a living, it's sometimes a very grotesque process. I'm entirely pro-choice.
I wouldn't butcher animals for a living, it's often quite a disgusting process as far as I'm concerned. I have no problem with other people doing so. And I have no problem with eating a steak. That's not contradictory or hypocritical.
I also would never want to be a nurse. I fully understand what nurses do. The human body can be quite disgusting at times. I'm glad nurses exist.
Such things are not contradictory. You can find an action and outcome acceptable, while not enjoying (or glorifying) all aspects of the process in question.
Once you cross the line of: all living things matter without exception and should never be killed, on to: some living things do not matter as much as others (eg plants for consumption) - then you're down to subjectivism as your argument across the board.
The animal rights argument is entirely subjective (what should the protections be, should there be any protections, how many should there be, who decides, for which living things, and on and on). What that means is, the opposite position has as much validity, it's also subjective. What it comes down to is majority politics ultimately: how many people can you get to agree with you, such that you can pass legislation in your preferred direction.
There's clearly a spectrum of consciousness between us and insects, there is no one clear-cut threshold, and some people are lower on it than some animals (see some neurological problems). Therefore arbitrarily deciding to put a strict care/don't care threshold on a species border is irrational. It makes much more sense to have a care/don't care spectrum, and not to limit it to one species.
I’m not so sure its clear that there’s a spectrum of consciousness. We have no way to observe consciousness (other than our own). For all we know, ants (or even trees or rocks) might well be just as conscious as us. We don’t have any evidence that they are, but that’s largely true of mammals and even other humans too.
> The animal rights argument is entirely subjective (…). What that means is, the opposite position has as much validity, it's also subjective.
The subjective aspects of a difficult question doesn’t mean all takes are equally valid. That’s the same as giving up and saying that nothing means anything.
My brother was researching brain regeneration in rats, and he said they used cryogenically induced lesions as a test bed. So probably something similar.
> The therapy also induces myelin to rebuild around axons and reduces glial scarring, which acts as a physical barrier that prevents the spinal cord from healing
This gives the impression that this would need to be administered before any scaring takes place. It is probably not a remedy for people with old injuries.
This, however, seems to suggest that the therapy actually reduces pre-existing scar tissue:
> the breakthrough therapy dramatically improved severely injured spinal cords in five key ways: (1) The severed extensions of neurons, called axons, regenerated; (2) scar tissue, which can create a physical barrier to regeneration and repair, significantly diminished;
Yeah, but this is incredible if it works at the human level.
My friend was in a car accident and a subwoofer that wasn't tied down ended up striking in him the back paralyzing him from the mid-back down. Years and years of heartache for both my friend, and the other friend who installed the subwoofer without tying it down.
There was a lot of things wrong that allowed this to happen, but knowing future people with injuries like my friend whom this therapy could save or alleviate makes me incredibly excited.
If scar tissue forms after an injury and blocks the area (on both sides of the nerve, I assume), like this ---x x--- . Could you then cut the scarred area away, creating "new" injury that this treatment could cure?
I remember reading a story many years ago a about a boy that got a nerve severed and later they opened the wound to remove the scar in the nerve and reconnect the nerve, so it regrows. The problem was that after cutting the scar, the nerve was shorter, so they have to take a shortcut in the elbow.
Cool! I am glad that it might be possible and that this might even be able to help those who have old injuries then!
My wife has internal scarring and adhesion(filaments of scar tissues) from appendicitis. This causes complications and her intestines can get twisted instead of moving freely over each other like they normally would. I asked if the adhesion could be cut to allow free movement but unfortunately it's sort of like a hydra, you cut one and it will form more/new adhesions.
I've always wondered... and so far have been unable to Google this: Does the non-nucleus part of a severed nerve cell die? If so, that would mean we only have a small window to "rejoin" severed CNS nerve cells, right? Nerve cells can be very long, I think up to a meter. I'd assume this includes spinal nerve cells of the CNS, which don't regrow. If the cells are severed, like in a spinal injury, that means there's a half-cell fragment with a nucleus, and the other half is the axon that's been cut away without a nucleus. Wouldn't the fragment without a nucleus shrivel up and die? That would be my intuition because I'd assume the nucleus is necessary to keep a cell alive.
Yep. The nerve soma(the cell body) does not die when the nerve is cut. The axon distal to the cut dies. The living axon tries to grow into the 'scaffold' of the axon part that died. This can take months and doesn't always restore full functionality.
so we just have to inject stem cells into the area where there are a lot of damaged nerve cells without nuclei and have these cells fuse with the damaged remnants. Just throw some PEG in there with the stem cells?
I find myself wondering whether a useful testing step between mice and people might be the community of small dogs with IVDD. French bulldogs, dachshunds, and corgis seem particularly susceptible and many of them wind up with rear paralysis. https://www.thedogsdown.com/how-can-ivdd-cause-paralysis/
My wife works on regenerative medicine for spine and they use dogs (and horses) a lot. Cells are similar and they suffer from the same problems. It's mostly dogs who die of natural causes though as dogs are too cute to experiment on...
You’d like to think that, but we’ve had multiple beagle rescues who would disagree. And they were the control population because the actual test subjects get killed.
The last section about generalizing the treatment is a bit underwhelming. Have they seen any evidence it can be used outside this sort of repair? What about for neuropathies, as from diabetes or surgeries? Stroke? Other dysfunctions (e.g. erectile/genital) having nervous system issues as a contributing factor?
Any treatment "might" have more general applicability--but surely there is some specific direction/class of these conditions that are indicated to be more appropriate to apply the treatment to than others. I wish they'd gone in more depth here.
A lot of cells will only grow when they feel familiar surroundings. This gel technique is used with various cell types. For example, pancreas cells will not grow alone in glass, but they will grow inside a specially-made gel that mimics their expected extra-cellular matrix [0].
These kind of studies and experiments always sound so amazing, but how long would something like this take to be applicable for at least human trials ?
I understand there are so many precautions to take etc, but is there any kind of 'complete consent' one could sign to jump start stuff like that ?
Would you, as a researcher, want to make your first attempts on human subjects? Even if someone gives you “complete consent”, it makes sense to ensure that that consent is informed and that those administering are prepared to give them care when things inevitably go wrong. At the very least, leaving all the ethical concerns aside, someone will have to pay for that care.
Nice, I've added a link to my calendar to check up on this work a year from now.
As described, it seems as though it would work just as well for traumatic brain injury as well. Either way it would be a huge boost in the quality of life for a lot of people.
I wonder if this would work with something like Guillaine-Barre syndrome (to wit, an autoimmune disease where the body attacks its own nerves, causing demyelination)
Over the last 25 years or so, there have been at least a dozen announcements of the latest miracle cure that works to repair spinal cord injury in mice. To date, none of them have translated to human efficacy. It's almost a meme at this point - like net-positive fusion being only ten years away. There appears to be a fundamental difference between mice and human nervous system injury repair modes that leads to early confidence. The spinal cords in mice essentially repair themselves if you so much as ask nicely.
The real litmus test for claims of effective spinal cord repair treatments is primate testing. If you see mice and not chimps, the treatment is probably a dead end.
Not to say this research doesn't have value - I fully support continued and rigorous research in this area - but hyperbolic claims like: "it works in mice, so it should also work in humans" aren't helping the cause.
"We are going straight to the FDA to start the process of getting this new therapy approved for use in human patients, who currently have very few treatment options.”
This is not a cheap process in terms of money and manpower. I think they probably have reason for confidence.
IIRC, the motor CNS in mammals is pretty similar across the board.
I thought the main point of mouse models was mostly to be a "first pass filter" for substances before moving onto other animals usually, sometimes humans if the straits are desperate enough. Cancer drugs in particular have little concern for long term side effects in their approval pipeline because the alternative may be having no long term.
First pass filters mean nothing when it comes to humans. 95% of all "stuff that works on mice" fails miserably on humans. We should treat such announcements with extreme skepticism.
I would guess things like how nerves and bones work is more similar across species than, say, how drugs might work on the brain, where a mouse brain is a hell of a lot different to human. Is that a reasonable assumption?
I was wondering the same thing. Pluses and minuses...
Rodents represent readily available models that can be used for a deeper understanding of basic biological mechanisms and for proof of concept for preclinical research hypotheses. However, attempts at direct clinical translation to humans have proven problematic or even impossible to date, principally due to issues of scaling and complexity.
I'm not an expert, but I guess this part is similar enough in mice and human to be optimistic. But IIUC the treatment only makes the regrow of the cut axons faster, it does not reconnect one part with the other part. So the time you should wait until the axon grows to the initial length in humans will be much longer than in mice.
"yet another headline that assumes that mice models have any bearing on humans". It's actually the other way around, very rarely do mice models results replicate in humans.
...as if some sort of future rodent time travelers went back in earth's pre-history and tasked countless human-filled labs with unlocking the secrets of rodent medical science so they could, in their own time, mine the wisdom of the ancients and ensure their immortality.
Recently every thread on HN about life and death has been devolving into a debate with people who insist that these things need to be addressed in the comments and those that simply don't care. It's honestly exhausting.
It's sort of like making food and having someone at the table try to discuss the morality of the meat you're using.... Except it's every. single. time.
Lab mice are killed off everyday after experiments end even if there's nothing wrong with them. Excuse me if I don't lose any sleep over this experiment.
A provocative and bad argument in favor of animal experimentation I heard is: "Animal experiments increase our life by X years. What each does with this extra time is a personal question."
Who cares if it’s every single time? It’s not exactly a feat of mental endurance to handle it.
I have a mental debate about animal-based testing/clothes/food on a regular basis, as I do about many choices I make that have a potential moral cost. I still often make those choices, and I don’t lose sleep over it. However, I believe regularly questioning one’s own viewpoints, habits and situation is a strength.
The assumption that it’s being done simply to draw attention is an unreasonable and condescending dismissal.
It’s a sanity check. Can we afford to not do X? because thank God there is some commonality in disgust. Clearly not at the moment, but I doubt even the original authors of those comments care more than you do.
I mean, that's 99% of internet comments. There are many topics I disagree with the HN majority (or vocal minority) on, and it becomes tiresome to see the same old stuff rehashed in every article when it's mostly off topic. But if we didn't allow people to comment unless they were genuinely open to having their mind changed about something, there would be no comments.
If you debate someone on the internet, you will never change their mind. But you might influence the opinion of someone else who reads your comments, and that's the best you can hope for.
Also, when a large number of people are wrong about something, there is often an opportunity of some kind associated with that. An investing opportunity, a career opportunity, a startup opportunity. When you see what others don't it can be a big advantage. So, embrace it.
You said in your first comment it "devolves into a debate." Now you're saying there is no debate. Poor consistency/word choice also lowers the value of HN discussion.
My grandfather is a paraplegic, and man how much I hope this isn't just faery dust.